scholarly journals Effect of parathyroid hormone on phospholipid metabolism in osteoblast-like rat osteogenic sarcoma cells

1986 ◽  
Vol 236 (2) ◽  
pp. 605-608 ◽  
Author(s):  
T Matsumoto ◽  
K Morita ◽  
Y Kawanobe ◽  
E Ogata
Keyword(s):  
Parathyroid Hormone ◽  
Osteogenic Sarcoma ◽  
Phospholipid Metabolism ◽  
Time Dependent ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Maximal Dose ◽  
Sarcoma Cells ◽  
Umr 106 ◽  
Stimulation Of

Previous results have shown that 1,25-dihydroxycholecalciferol [1,25(OH)2D3] enhances the synthesis of phosphatidylserine (PS) and suppresses the synthesis of phosphatidylethanolamine (PE) in osteoblast-like rat osteogenic sarcoma UMR 106 cells [Matsumoto, Kawanobe, Morita & Ogata (1985) J. Biol. Chem. 260, 13704-13709]. In the present study, the effect of parathyroid hormone (PTH) on phospholipid metabolism is examined by using these cells. Treatment of UMR 106 cells with human PTH-(1-34)-peptide suppresses the synthesis of phosphatidylethanolamine in a dose- and time-dependent manner without affecting the synthesis of PS. The maximal effect on PE synthesis is obtained with 2.4 nM-human PTH-(1-34)-peptide when the cells are treated for 48 h or longer. In addition, when human PTH-(1-34)-peptide is added together with the maximal dose of 1,25(OH)2D3, there is a further decline in PE synthesis, whereas the stimulation of PS synthesis by 1,25(OH)2D3 is not altered. Because methylation of PE is suggested to affect hormone receptor-adenylate cyclase coupling, the observed change in PE metabolism by PTH and 1,25(OH)2D3 may be, at least in part, involved in the development of desensitization phenomenon to PTH in these cells.

Parathyroid hormone depresses cytosolic pH and DNA synthesis in osteoblast-like cells

1988 ◽  
Vol 255 (1) ◽  
pp. E9-E15 ◽  
Author(s):  
I. R. Reid ◽  
R. Civitelli ◽  
L. V. Avioli ◽  
K. A. Hruska
Keyword(s):  
Growth Factors ◽  
Parathyroid Hormone ◽  
Thymidine Incorporation ◽  
Potent Inhibitor ◽  
Cell Communication ◽  
Maximal Effect ◽  
Maximal Dose ◽  
Cytosolic Ph ◽  
Fluid Compartment ◽  
Umr 106

It has recently become apparent that a number of hormones and growth factors modulate cytosolic pH (pHi), and there is some evidence that this in turn may influence cell growth. We have examined the effects of parathyroid hormone (PTH) on both these parameters in an osteoblast-like cell line, UMR 106. Preliminary studies, using the pH-sensitive fluorescent probe 2',7'-bis(2-carboxyethyl)-5(6)-carboxyfluorescein indicated that these cells regulate pHi by means of an amiloride-inhibitable Na+-H+ exchanger. Rat PTH-(1-34) (rPTH) caused a progressive dose-related decrease in pHi with a half-maximal effect at 10(-11) M. At 1 h, the maximal depression of pHi was 0.1 +/- 0.01 U. This effect was reproduced by forskolin, but neither agent influenced pHi in the presence of amiloride. Incorporation of [3H]thymidine was reduced by rPTH (half-maximal dose approximately 10(-11) M), forskolin, and N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate. The diacylglycerol analogue, phorbol 12-myristate 13-acetate, increased both pHi and [3H]thymidine incorporation, and amiloride reduced both indexes. However, rPTH remained a potent inhibitor of [3H]thymidine incorporation in the presence of amiloride, even though it did not affect pHi in these circumstances. It is concluded that PTH decreases pHi and growth in UMR 106 cells but that these changes can be dissociated. Depression of pHi may have other important effects on bone metabolism, such as reducing cell-cell communication, and may be associated with alkalinization of the bone fluid compartment.

Parathyroid hormone stimulation of the Na+/K+ pump in rat clonal osteosarcoma cells

1986 ◽  
Vol 111 (1) ◽  
pp. 61-66 ◽  
Author(s):  
M. De Luise ◽  
M. Harker
Keyword(s):  
Parathyroid Hormone ◽  
Adenylate Cyclase ◽  
Osteogenic Sarcoma ◽  
Monovalent Cation ◽  
Prostaglandin E ◽  
Adenylate Cyclase System ◽  
Pump Activity ◽  
Umr 106 ◽  
Insight Into ◽  
Stimulation Of

ABSTRACT A clonal line of osteoblastic cells from a rat osteogenic sarcoma (UMR 106–06), known to possess parathyroid hormone (PTH)-responsive adenylate cyclase, has been shown to increase its rate of K+ uptake mediated by a Na+/K+ pump after exposure to the hormone. The increase in pump activity was not associated with significant changes in K+ efflux or Na+ influx and would therefore be expected to alter intracellular levels of both Na+ and K+. The maximal (75%) increase in pump activity was noted at a PTH concentration of 100 μg/l and half-maximal stimulation at 1·9 μg/l. The effect appeared to be independent of the adenylate cyclase system, since a synthetic peptide antagonist of PTH activation of adenylate cyclase failed to prevent stimulation of the Na+/K+ pump. Similarly, prostaglandin E2, an alternative agonist of adenylate cyclase in these cells, had no effect on the Na+/K+ pump. This novel action of PTH on monovalent cation transport in osteoblast-like cells should provide a clearer insight into the mechanisms of hormone-induced bone resorption. J. Endocr. (1986) 111, 61–66

Modulation of glucose transport by parathyroid hormone and insulin in UMR 106–01, a clonal rat osteogenic sarcoma cell line

1995 ◽  
Vol 14 (2) ◽  
pp. 263-275 ◽  
Author(s):  
D M Thomas ◽  
S D Rogers ◽  
M W Sleeman ◽  
G M Pasquini ◽  
F R Bringhurst ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Cell Line ◽  
Glucose Transport ◽  
Transport System ◽  
Osteogenic Sarcoma ◽  
Regulatory Subunit ◽  
Sarcoma Cell ◽  
Sarcoma Cell Line ◽  
Glucose Transport System ◽  
Umr 106

ABSTRACT This study characterizes the actions of insulin and parathyroid hormone (PTH) on the glucose transport system in the rat osteogenic sarcoma cell line UMR 106–01, which expresses a number of features of the osteoblast phenotype. Using [1,2-3H]2-deoxyglucose (2-DOG) as a label, UMR 106–01 cells were shown to possess a glucose transport system which was enhanced by insulin. In contrast, PTH influenced glucose transport in a biphasic manner with a stimulatory effect at 1 h and a more potent inhibitory effect at 16 h on basal and insulin-stimulated 2-DOG transport. To explore the mechanism of PTH action, a direct agonist of cAMP-dependent protein kinase (PKA) was tested. 8-Bromo-cAMP had no acute stimulatory effect but inhibited basal and insulin-stimulated 2-DOG transport at 16 h. This result suggested that the prolonged, but not the acute, effect of PTH was mediated by the generation of cAMP. Further studies with the cell line UMR 4–7, a UMR 106–01 clone stably transfected with an inducible mutant inactive regulatory subunit of PKA, confirmed that the inhibitory but not the stimulatory effect of PTH was mediated by the PKA pathway. Northern blot data indicated that the prolonged inhibitory effects of PTH and 8-bromo-cAMP on glucose transport were likely to be mediated in part by reduction in the levels of GLUT1 (HepG2/brain glucose transporter) mRNA.

Direct effect of parathyroid hormone on insulin secretion from pancreatic islets

1990 ◽  
Vol 258 (6) ◽  
pp. E975-E984 ◽  
Author(s):  
G. Z. Fadda ◽  
M. Akmal ◽  
L. G. Lipson ◽  
S. G. Massry
Keyword(s):  
Insulin Secretion ◽  
Parathyroid Hormone ◽  
Pancreatic Islets ◽  
Insulin Release ◽  
Direct Effect ◽  
Indirect Evidence ◽  
Cytosolic Calcium ◽  
Dependent Manner ◽  
Stimulation Of

Indirect evidence indicates that parathyroid hormone (PTH) interacts with pancreatic islets and modulates their insulin secretion. This property of PTH has been implicated in the genesis of impaired insulin release in chronic renal failure. We examined the direct effect of PTH-(1-84) and PTH-(1-34) on insulin release using in vitro static incubation and dynamic perifusion of pancreatic islets from normal rats. Both moieties of the hormone stimulated in a dose-dependent manner glucose-induced insulin release but higher doses inhibited glucose-induced insulin release. This action of PTH was modulated by the calcium concentration in the media. The stimulatory effect of PTH was abolished by its inactivation and blocked by its antagonist [Tyr-34]bPTH-(7-34)NH2. PTH also augmented phorbol ester (TPA)-induced insulin release, stimulated adenosine 3',5'-cyclic monophosphate (cAMP) generation by pancreatic islets, and significantly increased (+50 +/- 2.7%, P less than 0.01) their cytosolic calcium. Verapamil inhibited the stimulatory effect of PTH on insulin release. The data show that 1) pancreatic islets are a PTH target and may have PTH receptors, 2) stimulation of glucose-induced insulin release by PTH is mediated by a rise in cytosolic calcium, 3) stimulation of cAMP production by PTH and a potential indirect activation of protein kinase C by PTH may also contribute to the stimulatory effect on glucose-induced insulin release, and 4) this action of PTH requires calcium in incubation or perifusion media.

scholarly journals Adrenaline Stimulation of Phospholipid Metabolism in Adipocyte Ghosts

1987 ◽  
Vol 40 (4) ◽  
pp. 405
Author(s):  
David Mann ◽  
Audrey M Bersten
Keyword(s):  
Fatty Acids ◽  
Arachidonic Acid ◽  
Linoleic Acid ◽  
Adenylate Cyclase ◽  
Phospholipid Metabolism ◽  
Dependent Manner ◽  
Long Chain Fatty Acids ◽  
Membrane Phospholipids ◽  
Dose Dependent ◽  
Stimulation Of

The incorporation of long-chain fatty acids into phospholipids has been detected in adipocyte ghosts that were incubated with [1_14 C] stearic, [1_14 C] linoleic or [l_14C] arachidonic acid. Adrenaline and adenosine activated this incorporation within 15 s of exposure of the ghosts to the hormones and the response was dose dependent. Maximum incorporation of labelled linoleic acid occurred at 10-5 M adrenaline and 10-7 M adenosine. The a-agonist phenylephrine and the ~-agonist isoproterenol were also shown to stimulate the incorporation of fatty acid in a dose dependent manner. Phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol were each labelled preferentially with linoleic or arachidonic acid. p-Bromophenacylbromide, quinacrine and centrophenoxine inhibited the adrenaline-stimulated incorporation of fatty acids into ghost membrane phospholipids, and p-bromophenacylbromide also reduced the activation of adenylate cyclase by adrenaline. NaF, an activator of adenylate cyclase, like adrenaline, stimulated the incorporation of linoleic acid into ghost membrane phospholipids.

Effects of Parathyroid Hormone and Insulin on Proliferation in Osteogenic Sarcoma UMR-106-01 Cells

1998 ◽  
Vol 33 (2) ◽  
pp. 466
Author(s):  
Kyung Moon ◽  
Choon Sung Lee ◽  
Jae Suk Chang ◽  
Key Yong Kim ◽  
Seong Who Kim ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Osteogenic Sarcoma ◽  
Umr 106

scholarly journals Stimulation of plasmin activity by oleic acid

1992 ◽  
Vol 282 (3) ◽  
pp. 863-866 ◽  
Author(s):  
A A R Higazi ◽  
Z Finci-Yeheskel ◽  
A A R Samara ◽  
R Aziza ◽  
M Mayer
Keyword(s):  
Oleic Acid ◽  
Binding Sites ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Plasmin Activity ◽  
Concentration Dependent Manner ◽  
Acid Analogue ◽  
Kinetic Pattern ◽  
Fold Stimulation ◽  
Stimulation Of

The amidolytic activity of plasmin with the chromogenic substrate H-D-valyl-L-leucyl-L-lysine p-nitroanilide (S-2251) is stimulated by oleic acid in a dose-dependent and saturable fashion. The activity of plasmin on S-2251 in the presence of oleic acid followed a sigmoidal kinetic pattern, with an almost 4-fold stimulation of activity at 60 microM-oleic acid. Half-maximal stimulation occurred at an oleic acid level of 19.5 microM. The amino acid analogue 6-aminohexanoic acid (AHA), which is known to bind to lysine-binding sites in plasmin, suppressed the stimulatory effect of oleic acid in a concentration-dependent manner; at 0.3 mM-AHA, about 70% of the oleic acid-dependent enhancement of plasmin activity was abolished. The l/v versus 1/[S] plot for plasmin changed in the presence of oleic acid from a linear to a non-linear curve, suggesting positive co-operativity. 14C-labelled oleic acid bound to plasmin, and the bound ligand was displaced by an excess of unlabelled oleic acid. Oleic acid also produced a marked (40-fold) stimulation of the plasminogen-dependent cleavage of S-2251 by urokinase. A half-maximal effect on plasminogen activation was obtained at 40 microM-oleic acid. The present findings suggest that the ability of oleic acid to stimulate plasmin activity and to enhance the conversion of plasminogen to plasmin depends on the interaction of oleic acid with specific lysine-binding sites in plasmin.

scholarly journals Parathyroid Hormone Inhibits Collagen Synthesis at Both Ribonucleic Acid and Protein Levels in Rat Osteogenic Sarcoma Cells

1989 ◽  
Vol 3 (2) ◽  
pp. 232-239 ◽  
Author(s):  
Nicola C. Partridge ◽  
Christi A. Dickson ◽  
Katja Kopp ◽  
Steven L. Teitelbaum ◽  
Edmond C. Crouch ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Ribonucleic Acid ◽  
Collagen Synthesis ◽  
Osteogenic Sarcoma ◽  
Protein Levels ◽  
Sarcoma Cells

Mechanism of insulin-induced activation of Na(+)-K(+)-ATPase in isolated rat soleus muscle

1991 ◽  
Vol 261 (2) ◽  
pp. C224-C230 ◽  
Author(s):  
E. Weil ◽  
S. Sasson ◽  
Y. Gutman
Keyword(s):  
Soleus Muscle ◽  
Time Course ◽  
Maximal Effect ◽  
Dependent Manner ◽  
Insulin Stimulation ◽  
K Uptake ◽  
Sequence Of Events ◽  
Rat Soleus Muscle ◽  
Isolated Rat ◽  
Stimulation Of

Insulin augments Na(+)-K(+)-ATPase activity in skeletal muscles. It has been proposed that the sequence of events is activation of Na(+)-H+ antiporter, increased intracellular Na+ concentration ( [Na+]i), and stimulation of Na(+)-K+ pump. We have used isolated rat soleus muscles to test this hypothesis. Insulin increased the ouabain-suppressible K+ uptake in a dose- and time-dependent manner. The maximal effect was observed at 50-100 mU/ml insulin. Stimulation of K+ uptake was accompanied by increased specific [3H]ouabain binding and lowered [Na+]i. The ionophore monensin, which promotes Na(+)-H+ exchange, also increased the rate of ouabain-suppressible K+ uptake in soleus muscle, with a maximal effect obtained at 10-100 microM ionophore. However, this increase was accompanied by an elevation of [Na+]i. In the presence of 10-100 microM monensin, addition of 100 mU/ml insulin further increased K+ uptake but reduced [Na+]i. The effect on K+ uptake was additive. Ouabain (10(-3) M) completely suppressed the effect of insulin on [Na+]i. Insulin had no effect on the magnitude or the time course of insulin stimulation of K+ uptake. Thus equal stimulation of Na(+)-K(+)-ATPase by insulin was observed when [Na+]i was elevated (under monensin) or lowered (under amiloride). These data suggest that activation of Na(+)-K(+)-ATPase in soleus muscle by insulin is not secondary to stimulation of Na(+)-H+ antiporter.

scholarly journals Stimulation of the human neutrophil respiratory burst by formyl peptides is primed by a protein kinase inhibitor, staurosporine

Blood ◽  
1993 ◽  
Vol 82 (9) ◽  
pp. 2890-2898 ◽  
Author(s):  
C Combadiere ◽  
J el Benna ◽  
E Pedruzzi ◽  
J Hakim ◽  
A Perianin
Keyword(s):  
Protein Kinase ◽  
Respiratory Burst ◽  
Phorbol Esters ◽  
Kinase Inhibitor ◽  
Polymorphonuclear Neutrophils ◽  
Time Dependent ◽  
Signalling Pathways ◽  
Dependent Manner ◽  
Formyl Peptides ◽  
Stimulation Of

Abstract Stimulation of polymorphonuclear neutrophils (PMN) by phorbol esters or formyl peptides (fMLP) generates large quantities of superoxide anion, the so-called respiratory burst (RB), a phenomenon associated with intense phosphorylation of a 47-kD protein (p47 phox). Staurosporine, a potent protein kinase C (PKC) antagonist, inhibits both responses when PMN are stimulated by phorbol myristate acetate (PMA), suggesting a positive role of PKC. In this study, we reassessed these PMN responses in fMLP-stimulated cells and found that staurosporine had opposite effects depending on the duration of PMN treatment with staurosporine. Short PMN incubation (0.5 to 3 minutes) with 25 to 100 nmol/L staurosporine inhibited the fMLP-induced RB, whereas longer treatment (15 to 20 minutes) enhanced it by up to about 200% relative to controls. In contrast, the PMA-mediated RB was depressed by staurosporine in a time-dependent manner. A primed fMLP-induced RB was also observed after long (15 minutes) PMN treatment with 5 to 100 mumol/L H-7, whereas shorter treatment (5 minutes) resulted in a small decrease in RB. By contrast, the tyrosine kinase inhibitor genistein (2 to 80 mumol/L) depressed fMLP-induced RB whatever the duration of PMN treatment. Analysis of 32P-phosphorylated proteins in fMLP-stimulated cells showed that short PMN treatment (< 8 minutes) with staurosporine abolished the phosphorylation of the 47-kD protein, which was identified as p47 phox, whereas long treatment partially restored p47 phox phosphorylation up to approximately 50% of the control value. In PMA-stimulated PMN, phosphorylation was reduced in a time-dependent manner. Furthermore, the staurosporine-primed RB and the staurosporine- induced recovery of phosphorylation were inhibited by sphingosine but not by genistein. Thus, in addition to its known depressive effect, staurosporine markedly potentiated fMLP-stimulated RB as a function of the duration of PMN treatment. The restoration of p47 phox phosphorylation suggests that staurosporine may alter the interactions between different protein kinases, producing marked time-dependent changes in signalling pathways. These data emphasize the care that should be taken in interpreting data obtained using this kinase inhibitor that may, however, be helpful analyzing in signalling pathways.

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